Abstract

Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity. Therefore, the purpose of this study was to compare weight-matched obese male and female mice to determine if the sex-dependent health benefits remain when body weight is similar. The development of obesity in female mice receiving a high-fat diet was delayed; however, subsequent comparisons of weight-matched obese mice revealed greater adiposity in obese female mice. Despite excess adiposity and enlarged adipocyte size, obese females remained more glucose tolerant than weight-matched male mice, and this benefit was associated with increased expression of adiponectin and reductions in immune cell infiltration and oxidative stress in adipose tissue. Therefore, the protective benefits of estrogen persist in the obese state and appear to improve the metabolic phenotype of adipose tissue and the individual.